ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 2.9 | DOI: 10.1530/ey.16.2.9

Diabetes and obesity during pregnancy are associated with oxidative stress genotoxicity in newborns

Castilla-Peon MF, Medina Bravo PG, Sánchez-Urbina R, Gallardo-Montoya JM, Soriano-López LC & Coronel Cruz FM

J Perinat Med. 2019 Apr 24;47(3):347-353. doi: 10.1515/jpm-2018-0201.

This study measured 8-hydroxy-deoxyguanosine (8-OH-dG), a marker of DNA oxidative damage, in venous umbilical cord plasma from newborns of mothers with and without a diabetes diagnosis during pregnancy.

Adult offspring born to mothers with gestational diabetes mellitus (GDM) have an increased frequency of conditions associated with high cardiovascular risk, such as obesity, insulin resistance, hypertension and other pro-atherosclerotic risk factors. However, the mechanisms underlying these observation are unknown. Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant mechanisms. Oxidative stress is increased in individuals with all types of diabetes including GDM. Oxidative stress leads to deoxynucleic acid (DNA) damage (genotoxicity) a phenomenon that has been linked to the development of some cardiovascular risk conditions and other age-related diseases. Fetuses of women with GDM are exposed to high oxidative stress and animal studies suggest that oxidative stress genotoxicity might be increased as well. Adult offspring of mothers with type 2 diabetes mellitus exhibit higher levels of the genotoxicity biomarker, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-OH-dG) than controls without a family history of DM. 8-OH-dG has been extensively used as a biomarker of oxidative stress genotoxicity in diabetes and other diseases and 8-OH-dG from umbilical cord venous blood has been used as a biomarker of fetal oxidative stress.

In this study, the levels of 8-OH-dG were higher in the offspring born to mothers with diabetes diagnosed during pregnancy than in women without diabetes, regardless of other confounding variables, such as maternal pre-gestational weight, HbA1c levels at the end of pregnancy, and age of the mother, and mode of delivery. It is possible that oxidative DNA damage may be a mechanism that increases the risk for age-related conditions in the offspring of women with GDM and/or obesity. The cross-sectional design of this study did not allow for inferring the causal relations between diabetes and/or overweight and oxidative stress or genotoxicity in the newborns. If more evidence from longitudinal studies supports this cause-effect theory, interventions aimed at reducing oxidative stress or promoting DNA repair could be investigated to evaluate their effect on the health of offspring. The authors suggest that following up newborns with high 8-OH-dG levels at birth could be useful to monitor the long-term development of cardiovascular diseases.

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